This application-proposes continuation of experiments designed understanding of the regulation and control of electrolyte transport large intestine. We plan to characterize the properities of Na-H exchange that is present in normal rats and identify the mechanism of electroneutral Cl absorption. We will also establish a basolateral membrane vesicle preparation to define the mechanism of sodium exit from the coloncyte. Primary emphasis is directed to defining the mechanism by which sodium and chloride absorption is enhanced by short chain fatty acids (SCFA) and by corticosteroids. The ability of the colon to increase fluid and electrolyte absorption can represent an important method to compensate for altered small intestinal function. These studies will establish the mechanism of SCFA absorb-tion and how SCFA stimulate active sodium and chloride absorption and test the hypothesis that SCFA are absorbed by non-ionic diffusion of the protonated form, followed by its disassociation and the coupling of NaH and Cl-SCFA exchanges. It is well established that corticosteroids stimulate active sodium and chloride transport but there is uncertainty whether the action of glucocorticoids manifest distinct (i.e. from aldosterone) receptor specific effects on ion transport. These studies will identify the ion transport changes that aldosterone induces in the apical membrane of the rat distal colony and will determine whether glucocorticoids produce receptor- specific changes in electrolyte transport (and whether electroneutral Na-Cl absorption is exclusively controlled by glucocorticoids. Since sodium depletion induces an increase in electroneutral sodium-chloride absorption (not electrogenic Na absorption, as found in ths distal colon), we plan to establish whether aldosterone (or glucocorticoids) enhance this electroneutral Na absorptive process. Further, we plan to establish the nature of Dl-dependent Na-H exchange in this segment. We also plan to obtain colonic mucosa from organ donors and prepare apical membrane vesicles in order to identify mechanism of Na uptake across the luminal membrane of human large intestine. In studies, we will determine ion transport by measuring both unidirectional --Na and fluxes across isolated intact mucosa from the rat distal (and proximal) colon under voltage clamp conditions and ion uptake by apical and basolateral membranes prepared from rat distal colon and human large intestine from organ donors.